def score(self, ligands, protein=None):
"""Automated scoring procedure.
Parameters
----------
ligands: iterable of oddt.toolkit.Molecule objects
Ligands to score
protein: oddt.toolkit.Molecule object or None
Protein object to be used. If None, then the default
one is used, else the protein is new default.
Returns
-------
ligands : array of oddt.toolkit.Molecule objects
Array of ligands (scores are stored in mol.data method)
"""
if protein:
self.set_protein(protein)
if not self.protein_file:
raise IOError("No receptor.")
if is_molecule(ligands):
ligands = [ligands]
ligand_dir = mkdtemp(dir=self.tmp_dir, prefix='ligands_')
output_array = []
for n, ligand in enumerate(ligands):
check_molecule(ligand, force_coords=True)
ligand_file = write_vina_pdbqt(ligand, ligand_dir, name_id=n)
try:
scores = parse_vina_scoring_output(
subprocess.check_output([
self.executable, '--score_only', '--receptor',
self.protein_file, '--ligand', ligand_file
] + self.params,
stderr=subprocess.STDOUT))
except subprocess.CalledProcessError as e:
sys.stderr.write(e.output.decode('ascii'))
if self.skip_bad_mols:
continue
else:
raise Exception('Autodock Vina failed. Command: "%s"' %
' '.join(e.cmd))
ligand.data.update(scores)
output_array.append(ligand)
rmtree(ligand_dir)
return output_array
def score(self, ligands, protein=None):
"""Automated scoring procedure.
Parameters
----------
ligands: iterable of oddt.toolkit.Molecule objects
Ligands to score
protein: oddt.toolkit.Molecule object or None
Protein object to be used. If None, then the default
one is used, else the protein is new default.
Returns
-------
ligands : array of oddt.toolkit.Molecule objects
Array of ligands (scores are stored in mol.data method)
"""
if protein:
self.set_protein(protein)
if not self.protein_file:
raise IOError("No receptor.")
if is_molecule(ligands):
ligands = [ligands]
ligand_dir = mkdtemp(dir=self.tmp_dir, prefix='ligands_')
output_array = []
for n, ligand in enumerate(ligands):
check_molecule(ligand, force_coords=True)
ligand_file = write_vina_pdbqt(ligand, ligand_dir, name_id=n)
try:
scores = parse_vina_scoring_output(
subprocess.check_output([self.executable, '--score_only',
'--receptor', self.protein_file,
'--ligand', ligand_file] + self.params,
stderr=subprocess.STDOUT))
except subprocess.CalledProcessError as e:
sys.stderr.write(e.output.decode('ascii'))
if self.skip_bad_mols:
continue
else:
raise Exception('Autodock Vina failed. Command: "%s"' %
' '.join(e.cmd))
ligand.data.update(scores)
output_array.append(ligand)
rmtree(ligand_dir)
return output_array
def test_check_molecule():
assert_raises_regexp(ValueError, 'Molecule object', check_molecule, [])
ligand = next(oddt.toolkit.readfile('sdf', xiap_crystal_ligand))
check_molecule(ligand)
# force protein
protein = next(oddt.toolkit.readfile('pdb', xiap_protein))
assert_raises_regexp(ValueError,
'marked as a protein',
check_molecule,
protein,
force_protein=True)
protein.protein = True
check_molecule(protein, force_protein=True)
# force coordinates
mol = oddt.toolkit.readstring('smi', 'c1ccccc1')
assert_raises_regexp(ValueError,
'3D coordinates',
check_molecule,
mol,
force_coords=True)
mol.make3D()
check_molecule(mol, force_coords=True)
#assert_raises_regexp(ValueError, 'positional', check_molecule, mol, True)
mol = oddt.toolkit.readstring('sdf', '''mol_title
handmade
0 0 0 0 0 0 0 0 0 0999 V2000
M END
''')
assert_raises_regexp(ValueError,
'has zero atoms',
check_molecule,
mol,
non_zero_atoms=True)
def diverse_conformers_generator(mol,
n_conf=10,
method='confab',
seed=None,
**kwargs):
"""Produce diverse conformers using current conformer as starting point.
Returns a generator. Each conformer is a copy of original molecule object.
.. versionadded:: 0.6
Parameters
----------
mol : oddt.toolkit.Molecule object
Molecule for which generating conformers
n_conf : int (default=10)
Targer number of conformers
method : string (default='confab')
Method for generating conformers. Supported methods:
* confab
* ga
seed : None or int (default=None)
Random seed
mutability : int (default=5)
The inverse of probability of mutation. By default 5, which translates
to 1/5 (20%) chance of mutation. This setting only works with genetic
algorithm method ("ga").
convergence : int (default=5)
The number of generations with unchanged fitness, should the algorothm
converge. This setting only works with genetic algorithm method ("ga").
rmsd : float (default=0.5)
The conformers are pruned unless their RMSD is higher than this cutoff.
This setting only works with Confab method ("confab").
nconf : int (default=10000)
The number of initial conformers to generate before energy pruning.
This setting only works with Confab method ("confab").
energy_gap : float (default=5000.)
Energy gap from the lowest energy conformer to the highest possible.
This setting only works with Confab method ("confab").
Returns
-------
mols : list of oddt.toolkit.Molecule objects
Molecules with diverse conformers
"""
if __version__ < '2.4.0':
raise NotImplementedError('Diverse conformer generation is not '
'implemented in OpenBabel before 2.4.0.')
check_molecule(mol, force_coords=True)
mol_clone = mol.clone
if seed is not None:
rand = ob.OBRandom(True)
rand.Seed(seed)
if method == 'ga':
if not hasattr(ob, 'OBConformerSearch'):
raise ValueError('OpenBabel needs to be compiled with eigen to '
'perform conformer search.')
cs = ob.OBConformerSearch()
cs.Setup(
mol_clone.OBMol,
n_conf, # numConformers
n_conf * 2, # numChildren
kwargs.get('mutability', 5), # mutability
kwargs.get('convergence', 5)) # convergence
cs.Search()
cs.GetConformers(mol_clone.OBMol)
elif method == 'confab':
ff = pybel._forcefields['uff']
ff.Setup(mol_clone.OBMol)
ff.DiverseConfGen(
kwargs.get('rmsd', 0.5), # rmsd
kwargs.get('nconfs', 10000), # nconfs (initial)
kwargs.get('energy_gap', 5000.0), # energy_gap
False) # verbose
ff.GetConformers(mol_clone.OBMol)
else:
raise ValueError('Method %s is not implemented' % method)
out = []
for i in range(mol_clone.OBMol.NumConformers()):
if i >= n_conf:
break
mol_output_clone = mol_clone.clone
mol_output_clone.OBMol.SetConformer(i)
out.append(mol_output_clone)
return out
def test_check_molecule():
with pytest.raises(ValueError, match='Molecule object'):
check_molecule([])
ligand = next(oddt.toolkit.readfile('sdf', xiap_crystal_ligand))
check_molecule(ligand)
# force protein
protein = next(oddt.toolkit.readfile('pdb', xiap_protein))
with pytest.raises(ValueError, match='marked as a protein'):
check_molecule(protein, force_protein=True)
protein.protein = True
check_molecule(protein, force_protein=True)
# force coordinates
mol = oddt.toolkit.readstring('smi', 'c1ccccc1')
with pytest.raises(ValueError, match='3D coordinates'):
check_molecule(mol, force_coords=True)
mol.make3D()
check_molecule(mol, force_coords=True)
# with pytest.raises(ValueError, match='positional'):
# check_molecule(mol, True)
mol = oddt.toolkit.readstring(
'sdf', '''mol_title
handmade
0 0 0 0 0 0 0 0 0 0999 V2000
M END
''')
with pytest.raises(ValueError, match='has zero atoms'):
check_molecule(mol, non_zero_atoms=True)
def test_check_molecule():
with pytest.raises(ValueError, match='Molecule object'):
check_molecule([])
ligand = next(oddt.toolkit.readfile('sdf', xiap_crystal_ligand))
check_molecule(ligand)
# force protein
protein = next(oddt.toolkit.readfile('pdb', xiap_protein))
with pytest.raises(ValueError, match='marked as a protein'):
check_molecule(protein, force_protein=True)
protein.protein = True
check_molecule(protein, force_protein=True)
# force coordinates
mol = oddt.toolkit.readstring('smi', 'c1ccccc1')
with pytest.raises(ValueError, match='3D coordinates'):
check_molecule(mol, force_coords=True)
mol.make3D()
check_molecule(mol, force_coords=True)
# with pytest.raises(ValueError, match='positional'):
# check_molecule(mol, True)
mol = oddt.toolkit.readstring('sdf', '''mol_title
handmade
0 0 0 0 0 0 0 0 0 0999 V2000
M END
''')
with pytest.raises(ValueError, match='has zero atoms'):
check_molecule(mol, non_zero_atoms=True)
def dock(self, ligands, protein=None):
"""Automated docking procedure.
Parameters
----------
ligands: iterable of oddt.toolkit.Molecule objects
Ligands to dock
protein: oddt.toolkit.Molecule object or None
Protein object to be used. If None, then the default one
is used, else the protein is new default.
Returns
-------
ligands : array of oddt.toolkit.Molecule objects
Array of ligands (scores are stored in mol.data method)
"""
if protein:
self.set_protein(protein)
if not self.protein_file:
raise IOError("No receptor.")
if is_molecule(ligands):
ligands = [ligands]
ligand_dir = mkdtemp(dir=self.tmp_dir, prefix='ligands_')
output_array = []
for n, ligand in enumerate(ligands):
check_molecule(ligand, force_coords=True)
ligand_file = write_vina_pdbqt(ligand, ligand_dir, name_id=n)
ligand_outfile = ligand_file[:-6] + '_out.pdbqt'
try:
scores = parse_vina_docking_output(
subprocess.check_output([
self.executable, '--receptor', self.protein_file,
'--ligand', ligand_file, '--out', ligand_outfile
] + self.params + ['--cpu', str(self.n_cpu)],
stderr=subprocess.STDOUT))
except subprocess.CalledProcessError as e:
sys.stderr.write(e.output.decode('ascii'))
if self.skip_bad_mols:
continue # TODO: print some warning message
else:
raise Exception('Autodock Vina failed. Command: "%s"' %
' '.join(e.cmd))
# docked conformations may have wrong connectivity - use source ligand
if is_openbabel_molecule(ligand):
if oddt.toolkits.ob.__version__ >= '2.4.0':
# find the order of PDBQT atoms assigned by OpenBabel
with open(ligand_file) as f:
write_order = [
int(line[7:12].strip()) for line in f
if line[:4] == 'ATOM'
]
new_order = sorted(range(len(write_order)),
key=write_order.__getitem__)
new_order = [i + 1
for i in new_order] # OBMol has 1 based idx
assert len(new_order) == len(ligand.atoms)
else:
# Openbabel 2.3.2 does not support perserving atom order.
# We read back the PDBQT ligand to get "correct" bonding.
ligand = next(oddt.toolkit.readfile('pdbqt', ligand_file))
if 'REMARK' in ligand.data:
del ligand.data['REMARK']
docked_ligands = oddt.toolkit.readfile('pdbqt', ligand_outfile)
for docked_ligand, score in zip(docked_ligands, scores):
# Renumber atoms to match the input ligand
if (is_openbabel_molecule(docked_ligand)
and oddt.toolkits.ob.__version__ >= '2.4.0'):
docked_ligand.OBMol.RenumberAtoms(new_order)
# HACK: copy docked coordinates onto source ligand
# We assume that the order of atoms match between ligands
clone = ligand.clone
clone.clone_coords(docked_ligand)
clone.data.update(score)
# Calculate RMSD to the input pose
try:
clone.data['vina_rmsd_input'] = rmsd(ligand, clone)
clone.data['vina_rmsd_input_min'] = rmsd(
ligand, clone, method='min_symmetry')
except Exception:
pass
output_array.append(clone)
rmtree(ligand_dir)
return output_array
def dock(self, ligands, protein=None):
"""Automated docking procedure.
Parameters
----------
ligands: iterable of oddt.toolkit.Molecule objects
Ligands to dock
protein: oddt.toolkit.Molecule object or None
Protein object to be used. If None, then the default one
is used, else the protein is new default.
Returns
-------
ligands : array of oddt.toolkit.Molecule objects
Array of ligands (scores are stored in mol.data method)
"""
if protein:
self.set_protein(protein)
if not self.protein_file:
raise IOError("No receptor.")
if is_molecule(ligands):
ligands = [ligands]
ligand_dir = mkdtemp(dir=self.tmp_dir, prefix='ligands_')
output_array = []
for n, ligand in enumerate(ligands):
check_molecule(ligand, force_coords=True)
ligand_file = write_vina_pdbqt(ligand, ligand_dir, name_id=n)
ligand_outfile = ligand_file[:-6] + '_out.pdbqt'
try:
scores = parse_vina_docking_output(
subprocess.check_output([self.executable, '--receptor',
self.protein_file,
'--ligand', ligand_file,
'--out', ligand_outfile] +
self.params +
['--cpu', str(self.n_cpu)],
stderr=subprocess.STDOUT))
except subprocess.CalledProcessError as e:
sys.stderr.write(e.output.decode('ascii'))
if self.skip_bad_mols:
continue # TODO: print some warning message
else:
raise Exception('Autodock Vina failed. Command: "%s"' %
' '.join(e.cmd))
# docked conformations may have wrong connectivity - use source ligand
if is_openbabel_molecule(ligand):
if oddt.toolkits.ob.__version__ >= '2.4.0':
# find the order of PDBQT atoms assigned by OpenBabel
with open(ligand_file) as f:
write_order = [int(line[7:12].strip())
for line in f
if line[:4] == 'ATOM']
new_order = sorted(range(len(write_order)),
key=write_order.__getitem__)
new_order = [i + 1 for i in new_order] # OBMol has 1 based idx
assert len(new_order) == len(ligand.atoms)
else:
# Openbabel 2.3.2 does not support perserving atom order.
# We read back the PDBQT ligand to get "correct" bonding.
ligand = next(oddt.toolkit.readfile('pdbqt', ligand_file))
if 'REMARK' in ligand.data:
del ligand.data['REMARK']
docked_ligands = oddt.toolkit.readfile('pdbqt', ligand_outfile)
for docked_ligand, score in zip(docked_ligands, scores):
# Renumber atoms to match the input ligand
if (is_openbabel_molecule(docked_ligand) and
oddt.toolkits.ob.__version__ >= '2.4.0'):
docked_ligand.OBMol.RenumberAtoms(new_order)
# HACK: copy docked coordinates onto source ligand
# We assume that the order of atoms match between ligands
clone = ligand.clone
clone.clone_coords(docked_ligand)
clone.data.update(score)
# Calculate RMSD to the input pose
clone.data['vina_rmsd_input'] = rmsd(ligand, clone)
clone.data['vina_rmsd_input_min'] = rmsd(ligand, clone,
method='min_symmetry')
output_array.append(clone)
rmtree(ligand_dir)
return output_array
